Asrij depletion results in increased repopulation ability and affects hematopoietic recovery from stress. Floxed and KO cells were compared in all cases and are indicated in red and light green, respectively. (A) Schematic representation of the transplantation study. A total of 5 × 10⁶ BM cells harvested from 6-month-old (CD45.2⁺) asrij floxed or KO mice were injected into lethally irradiated (9.5 Gy) 2-month-old CD45.1 mice. These CD45.1 mice (primary transplants) were analyzed for PB cell counts at monthly intervals. Four months after transplantation, 1 × 10⁶ BM cells harvested from the primary transplants were injected into another set of lethally irradiated (9.5 Gy) CD45.1 recipients (secondary transplants), which were similarly analyzed. (B-G) Outcome of serial BMT assayed by analysis of (B,E) PB cell counts (n = 10 mice per genotype) at monthly intervals after transplant, (C,F) HSPC frequencies (n = 3 mice per genotype), and (D,G) spleen weights (n = 3 mice per genotype) at 4 months posttransplant. Mice that received KO BM had significantly increased WBC and platelet counts, HSPC frequencies and spleen weights than those that received asrij floxed BM. (D,G) Bar represents 1 cm. Statistically significant differences for PB cell counts, identified using repeated measures ANOVA, and for HSPC frequencies and spleen weights, identified using ANOVA: single factor analysis, are indicated. (H) Kaplan-Meier survival analysis of 2-month-old mice stressed with sublethal dosage of γ irradiation (6.5 Gy, n = 10 mice per genotype). ***P < .001, generalized Wilcoxon test. (I) PB cell count analysis after irradiation (n = 10 mice per genotype). (J) Flow cytometric analysis and quantification of HSPC frequencies after irradiation (n = 3 mice per genotype). (K) Representative Ki-67/7-AAD flow cytometric plots and quantification showing the cell-cycle distribution of HSCs after irradiation (n = 3 mice per genotype). (L) Kaplan-Meier survival analysis of 2-month-old mice stressed with 5-FU, weekly, for 3 weeks (150 mg/kg of mouse body weight, n = 10 mice per genotype). *P < .05, generalized Wilcoxon test. (M) PB cell count analysis after 5-FU treatment shows significantly reduced WBCs in KO mice as compared with floxed controls (n = 10 mice per genotype). Statistically significant differences for (I-K) identified using ANOVA: single factor analysis and for (M) identified using repeated measures ANOVA are indicated. Black arrow, time of stress administration to mice. Error bars denote standard error of mean. *P < .05, **P < .01, and ***P < .001.